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  • 1
    Electronic Resource
    Electronic Resource
    The overwhelming postsplenectomy sepsis problem (1980)
    Springer
    World journal of surgery 4 (1980), S. 423-427 
    Details
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La vulnérabilité à l’infection après splénectomie ne dépend ni de l’âge, ni de la maladie originelle. Toute infection survenant après splénectomie est une urgence qui peut tuer en quelques heures: elle exige donc un traitement immédiat et adéquat. La pathogénie est encore mal précisée. Des données expérimentales suggèrent que la perte du mécanisme de filtration splénique est plus importante que le déficit immunologique, ces deux facteurs pouvant cependant coexister. Il est apparemment impossible d’assurer une protection parfaite contre les infections graves après splénectomie. Mais certaines études expérimentales indiquent qu’on peut en réduire la fréquence par les nouvelles techniques chirurgicales qui évitent la splénectomie totale, par la vaccination antipneumococcique et par l’administration préventive de pénicilline. Lorsque les fonctions de la rate seront mieux connues, il sera possible de préciser le rôle prophylactique de l’autotransplantation splénique.
    Notes: Abstract Postsplenectomy vulnerability to infection is not limited to age or disease process. Postsplenectomy infection is an emergency problem that requires immediate and accurate treatment because death is potential within a few hours of onset. Although the pathogenesis of overwhelming postsplenectomy sepsis is not completely understood, experimental evidence suggests that loss of mechanical filtration is more important than immunologic deficiences resulting from splenectomy. Certainly, a combination of both may be present. While no single measure seems to completely protect against overwhelming postsplenectomy sepsis, experimental evidence suggests that by reducing or minimizing the amount of spleen removed by newer surgical techniques, and by the addition of pneumococcal vaccine and prophylactic penicillin, the incidence of overwhelming sepsis can be reduced. Further evaluation of splenic function is necessary to assess the role of autotransplantation in the prevention of postsplenectomy sepsis (Fig. 1).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02393164
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  • 2
    Electronic Resource
    Electronic Resource
    Experimental Animal Models for Studying Antimicrobial Pharmacokinetics in Otitis Media (1989)
    Springer
    Pharmaceutical research 6 (1989), S. 279-285 
    Details
    ISSN: 1573-904X
    Keywords: otitis media ; pharmacokinetics ; amoxicillin ; trimethoprim ; sulfamethoxazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Antimicrobial treatment of otitis media, especially drug dosing considerations, is largely empiric, with few reported pharmacologic studies of drug distribution into the middle ear. A chinchilla animal model of serous and purulent otitis media has been used for some time to investigate mechanisms of disease pathogenesis. This model was adapted to investigate the penetration of amoxicillin, trimethoprim, and sulfamethoxazole into middle ear effusion. Purulent otitis media was produced by direct middle ear inoculation with type 7F Streptococcus pneumoniae. Serous otitis media was produced by eustachian tube obstruction using silastic sponge or Coeflex cement, but the Coeflex caused an undesirable local inflammatory response. The three antibiotics were administered to chinchillas with serous and purulent middle ear effusion. Plasma and ear fluid drug concentrations were measured by liquid chromatography and demonstrated the value of this model in assessing antibiotic penetration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015938205892
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  • 3
    Electronic Resource
    Electronic Resource
    Comparison of Two Otitis Media Models for the Study of Middle Ear Antimicrobial Pharmacokinetics (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 855-859 
    Details
    ISSN: 1573-904X
    Keywords: otitis media ; pharmacokinetics ; amoxicillin ; sulfamethoxazole ; trimethoprim
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We compared two models of acute otitis media that estimate middle ear antimicrobial pharmacokinetics. Using a crossover study design, we compared a systemic drug administration model with a diffusion model we devised that measures the disappearance of antimicrobials from the middle ear. We induced acute otitis media in 14 chinchillas by inoculating S. pneumoniae into the middle ear, then administered 3 antimicrobials: amoxicillin, trimethoprim, and sulfamethoxazole. Next we collected middle ear fluid samples to analyze drug concentrations and compare rate constants for the systemic and diffusion models by analysis of variance. We found that amoxicillin K values were not affected by model testing sequence (p = 0.827) or model type (systemic versus diffusion, p = 0.310), nor were sulfamethoxazole K values: model testing sequence (p = 0.917), model type (p = 0.963). Trimethoprim K values were also not affected by model testing sequence (p = 0/760), but were by model type (p = 0.0001). Trimethoprim elimination from the diffusion model was faster (K = 0.33 ± 0.17 versus 0.57 ± 0.09 hr−1) than from the systemic model, although it appears this was caused by sampling before drug distribution into the middle ear was complete. In conclusion, it appears K values derived from either systemic antimicrobial administration or direct middle ear instillation are similar for assessing middle ear anitmicrobial pharmacokinetics, and these models can be used interchangeably to study factors affecting otitis media treatment response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018981808868
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of Streptococcus pneumoniae and Influenza A Virus on Middle Ear Antimicrobial Pharmacokinetics in Experimental Otitis Media (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 860-864 
    Details
    ISSN: 1573-904X
    Keywords: otitis media ; influenza A virus ; Streptococcus pneumoniae ; amoxicillin ; sulfamethoxazole ; trimethoprim ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Antimicrobial treatment failures in children with acute otitis media and concomitant viral respiratory tract infection prompted us to study the effects of influenza A virus infection on middle ear antimicrobial drug penetration. Using a chinchilla model of Streptococcus pneumoniae we compared middle ear elimination rates in 4 groups of chinchillas: (1) control, (2) influenza A virus inoculation alone intranasally, (3) both influenza A and S. pneumoniae inoculation directly into the middle ear, and (4) S. pneumoniae inoculation alone into the middle ear. After infection was established, a solution containing amoxicillin, sulfamethoxazole, and trimethoprim was instilled into the middle ear and removed 4 hours later. The rate constant of elimination and half-life were calculated from measured drug concentrations initially and at 4 hours. S. pneumoniae infection alone significantly shortened the middle ear elimination half-life compared with the control group: amoxicillin, 2.65 ± 0.73 vs. 6.63 ±  2.55 hr; sulfamethoxazole, 1.75 ± 0.28 vs. 2.74 ± 0.6 hr; and trimethoprim, 1.06 ±  0.14 vs. 1.56 ± 0.34 hr (n = 16 ears, p values all 〈0.01). The combined influenza virus and S. pneumoniae infection significantly lengthened the half-life compared with the S. pneumoniae infection alone: amoxicillin, 5.65 ± 6.44 vs. 2.65 ± 0.73 hr; sulfamethoxazole, 2.5 ± 0.85 vs. 1.75 ± 0.28 hr; and trimethoprim, 1.26 ± 0.42 vs. 1.06 ± 0.14 hr (n = 16 ears, p values all 〈0.01). Influenza virus produced the longest half-lives for all 3 antimicrobials: amoxicillin 25.52 ± 14.96 hr; sulfamethoxazole, 5.46 ± 0.87 hr; and trimethoprim, 2.57 ± 0.75 hr. These effects demonstrate that influenza and S. pneumoniae infections alone and together affect middle ear antimicrobial penetration. The decreased penetration of antimicrobials that occurred with the combined viral and bacterial infection vs. the bacteria alone supports the clinical observation that patients with infections caused by both organisms may have decreased middle ear antimicrobial concentrations, producing treatment failures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018933925707
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  • 5
    Electronic Resource
    Electronic Resource
    An Experimental Model for Measuring Middle Ear Antimicrobial Drug Penetration in Otitis Media (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 1242-1247 
    Details
    ISSN: 1573-904X
    Keywords: otitis media ; pharmacokinetics ; amoxicillin ; trimethoprim ; sulfamethoxazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Bacteria are an important cause of acute otitis media and successful treatment depends on achieving inhibitory or bacteriacidal antimicrobial drug concentrations in the middle ear. To evaluate further otitis media treatment success and failure, we developed a chinchilla model to study antimicrobial drug penetration through the middle ear mucosa. Using quantitative histomorphometry, we measured the middle ear space in 10 chinchillas and found a mean ±SD volume of 2.09 ± 0.08 ml and a mean SD surface area of 14.41 ± 1.48 cm2. To measure the apparent rate constant (K e) of antibiotic elimination from the middle ear, through the middle ear mucosa, an antibiotic solution was inoculated into the middle ear cavity, and samples were aspirated between 1 and 8 hr later. In normal ears, the mean K e ±SD for amoxicillin was 0.118 ± 0.013 hr−1, that for a trimethoprim 0.461 ± 0.090 hr−1, and that for sulfamethoxazole 0.265 ± 0.062 hr−1. In ears inoculated with type 7F Streptococcus pneumoniae to induce acute otitis media, the K e ±SD increased for all three drugs (P 〈 0.05): amoxicillin to 0.286 ± 0.089 hr−1, trimethoprim to 0.662 ± 0.118 hr−1, and sulfamethoxazole to 0.411 ± 0.056 hr−1. These values demonstrate that amoxicillin had the lowest apparent penetration rate constant of the three antibiotics but the greatest increase from normal to infected mucosa (142%). Trimethoprim had the highest apparent penetration rate constant of the three antibiotics but the smallest increase from normal to infected mucosa (44%), while the sulfamethoxazone apparent penetration rate constant increased from normal to infected mucosa by 55%. The K e for amoxicillin was the same for inoculation volumes of 0.8 and 1.6 ml (P = 0.557) and the same for sampling intervals of 4 and 8 hr (P = 0.054). All three antimicrobial drug concentration–time curves were log-linear, as predicted by Fick's first law of diffusion. In conclusion, this model overcomes the technical limitations of previous models and permits investigation of the many factors that can influence antibiotic penetration into the middle ear and reduce otitis media treatment efficacy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015977603224
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